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Precedia/Monoclonal antibodies/Isembyld/Efficacy evidence

Isembyld: animal efficacy model or human cells?

apitegromab · pro/latent myostatin

Check my plan vs. these

Efficacy evidence

SMA mouse model with muSRK-015P (apitegromab on a mouse IgG1 backbone) plus SMN splice modulator SMN-C1

“Inhibition of myostatin activation by muSRK-015P, the parenteral version of apitegromab on a mouse IgG1 backbone, in combination with a small molecule SMN splice modulator (SMN-C1), increased muscle size and function in a mouse model of SMA.”

✓ VerifiedFDA integrated review, p. 181Source ↗

Why that model

Myostatin at least 96% and the epitope 100% conserved across the five species tested, with similar binding (2-8 nM)

“showed binding to promyostatin from all five species with affinities between 2 and 8nM (Table 48). The sequence of myostatin is at least 96% conserved among these species, and the epitope for apitegromab within myostatin is 100% conserved among these species.”

✓ VerifiedFDA integrated review, p. 184Source ↗

Reviewer's view of the efficacy data

Not stated in public reviews

Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.

Same question, other monoclonal antibodies

Actemra

tocilizumab · IL-6R

Cynomolgus monkey collagen-induced arthritis model

Adakveo

crizanlizumab · P-selectin

Human cells in vitro: blockade of neutrophil rolling/adhesion and sickled red cell binding to human endothelium

Adbry

tralokinumab · IL-13

In vivo type-2 inflammation models (IL-13-induced mouse, monkey allergen challenge); no AD model; AD support from in vitro human skin cells

Aduhelm

aducanumab · Aggregated amyloid-β

Tg2576 transgenic AD mouse with murine analog ch12F6A (plaque and insoluble Aβ reduction)

Aimovig

erenumab · CGRP receptor

Capsaicin-induced dermal blood flow inhibition in normal cynomolgus monkeys; no animal migraine model

Ajovy

fremanezumab · CGRP

Rat post-concussion and medication-overuse headache models; vasodilation models in rat and cynomolgus monkey

Alhemo

concizumab · TFPI

Antibody-induced (anti-FVIII) hemophilia A rabbit cuticle bleeding model: dose-dependent reduction in blood loss

Andembry

garadacimab · Factor XIIa

Captopril-induced edema in heterozygous C1-INH-deficient mice: garadacimab inhibited vascular permeability increase

Anthim

obiltoxaximab · B. anthracis PA

Inhalational anthrax (aerosol B. anthracis spores) in NZW rabbits and cynomolgus macaques

Arzerra

ofatumumab · CD20

SCID mouse xenografts of human B-cell tumour lines treated with ofatumumab

Avastin

bevacizumab · VEGF-A

Human tumour xenografts in nude mice, mainly with murine parent A4.6.1; bevacizumab also inhibited breast, prostate and ovarian xenografts

Bavencio

avelumab · PD-L1

Syngeneic MC38 colon cancer mouse model with avelumab

Benlysta

belimumab · BLyS (BAFF)

B-cell reduction and inhibited splenocyte proliferation in normal mice and monkeys; no disease model

Beovu

brolucizumab · VEGF-A

Rodent ocular models: VEGF-induced retinal permeability (rat), oxygen-induced retinopathy (neonatal rat), laser-induced CNV (mouse)

Beyfortus

nirsevimab · RSV F protein

Cotton rat RSV A2/B9320 challenge model with antibody 1G7 (IM prophylaxis 1 day before infection)

Bimzelx

bimekizumab · IL-17A/IL-17F

In vitro only: primary human dermal fibroblasts and keratinocytes; no in vivo pharmacodynamics

Briumvi

ublituximab · CD20

In vivo B-cell depletion in mouse models clearing patient-derived B-CLL cells

Cablivi

caplacizumab · von Willebrand factor (A1 domain)

Baboon model of acquired TTP induced by an inhibitory anti-ADAMTS13 antibody (preventive and therapeutic dosing)

Campath

alemtuzumab · CD52

Lymphocyte depletion in huCD52 transgenic mice and cynomolgus monkeys

Cimzia

certolizumab pegol · TNF-α

Human TNFα challenge in normal mice and rabbits; transgenic mouse polyarthritis model (protection at 10 and 30 mg/kg)

Cinqair

reslizumab · IL-5

Allergen-challenge eosinophilia models: OVA-sensitized mice and guinea pigs, Ascaris-challenged monkeys, antigen-challenged rabbits

Cosentyx

secukinumab · IL-17A

Mouse knee-joint inflammation and air pouch models driven by locally produced human IL-17A; no psoriasis-like disease model

Crysvita

burosumab · FGF23

Hyp mouse (XLH model) treated with a murine anti-FGF23 antibody

Cyramza

ramucirumab · VEGFR2

Surrogate DC101 in human gastric cancer xenografts (NCI-N87, MKN-45) and primary gastric tumor fragments in athymic mice

Danyelza

naxitamab · GD2

Athymic nude mice bearing subcutaneous human neuroblastoma xenografts treated with naxitamab

Darzalex

daratumumab · CD38

Human lymphoma xenografts in SCID mice (preventive and therapeutic), plus in vitro human/patient-derived cell assays

Dupixent

dupilumab · IL-4Ra

Transgenic mice expressing human IL-4 and IL-4Rα in type 2 immune response models; no atopic dermatitis model

Ebanga

ansuvimab · Zaire ebolavirus glycoprotein

Lethal EBOV Kikwit challenge in rhesus monkeys: single 50 mg/kg up to 5 days postchallenge prevented mortality

Ebglyss

lebrikizumab · IL-13

Human IL-13-induced airway inflammation in C57BL/6 mice (lebrikizumab reduced inflammatory reactions)

Emgality

galcanezumab · CGRP

Capsaicin-induced dermal blood flow increase in normal rats and cynomolgus monkeys

Empliciti

elotuzumab · SLAMF7

Human myeloma xenografts (L363, OPM2) in immunodeficient mice treated with elotuzumab (HuLuc63)

Enflonsia

clesrovimab · RSV F protein (site IV)

Cotton rat intranasal RSV A2 challenge model dosed with clesrovimab (0.03-2.5 mg/kg)

Enjaymo

sutimlimab · Complement C1s

Near-complete classical complement inhibition (up to 98%) in cynomolgus monkeys at both dose levels

Enspryng

satralizumab · IL-6R

Normal cynomolgus monkeys: inhibition of IL-6-stimulated CRP production and soluble IL-6R binding (vs tocilizumab)

Entyvio

vedolizumab · α4β7-integrin

Spontaneous-colitis cotton-top tamarins treated with Act-1, the murine vedolizumab precursor (2.0 mg/kg for 8 days)

Erbitux

cetuximab · EGFR

Human tumour xenografts (GEO colon, renal, A431) in immunodeficient mice treated with cetuximab

Evenity

romosozumab · Sclerostin

Ovariectomized rat and monkey models of postmenopausal osteoporosis treated with romosozumab

Evkeeza

evinacumab · ANGPTL3

Evinacumab in hyperlipidemic mouse models (ApoE-/-, Ldlr-/-, db/db, high-fat diet) and normolipidemic mice

Exdensur

depemokimab · IL-5

Prolonged blood eosinophil suppression in normal cynomolgus monkeys (39-week PK/PD study, 1 mg/kg)

Fasenra

benralizumab · IL-5Rα

Naive and allergen-challenged cynomolgus monkeys: eosinophil depletion in blood, bone marrow and BAL fluid

Gamifant

emapalumab · IFN-γ

Perforin-deficient mice infected with LCMV (HLH model) treated with surrogate antibody XMG1.2

Gazyva

obinutuzumab · CD20

Human B-cell lymphoma xenografts (DLBCL, NHL, MCL) in SCID beige mice

Herceptin

trastuzumab · HER2

Human HER2-overexpressing tumour xenografts (BT-474) in vivo; trastuzumab plus paclitaxel gave greatest regression

Humira

adalimumab · TNF-α

Human TNFα transgenic arthritis mice (Tg197, Tg5453); hTNFα-induced lethality (mice) and pyrexia (rabbits)

Hympavzi

marstacimab · TFPI

Hemophilia A (FVIII-deficient) and B (FIX-deficient) mouse models; blood loss reduced 76% and 65%

Ilaris

canakinumab · IL-1β

Canakinumab inhibited human IL-1β-induced mouse joint inflammation, rat fever and mouse air-pouch neutrophil infiltration

Ilumya

tildrakizumab · IL-23 p19

Mouse surrogate SCH-900598 in T-cell-dependent and anti-CD40 colitis models; unrelated anti-IL-23p19 mAb in psoriasis skin xenograft mice

Imaavy

nipocalimab · FcRn

Nipocalimab in humanized FcRn Tg32 mice: collagen antibody-induced arthritis and immune thrombocytopenia models

Imfinzi

durvalumab · PD-L1

Durvalumab in A375 and HPAC human tumour xenografts with human CD4+/CD8+ T cells; HPAC max tumour growth inhibition 74%

Imjudo

tremelimumab · CTLA-4

Surrogate anti-mouse CTLA-4 antibody in subcutaneous syngeneic mouse tumour models, alone and with anti-mouse PD-L1

Jemperli

dostarlimab · PD-1

MC38 syngeneic mouse colon tumor model with anti-mouse PD-1 surrogate RMP1-14; dostarlimab tested in vitro only

Kevzara

sarilumab · IL-6R

Mouse collagen-induced arthritis with surrogate REGN844 (prophylactic); prevented joint inflammation and bone erosion

Keytruda

pembrolizumab · PD-1

MC38 syngeneic mouse colon tumor model with hamster anti-mouse PD-1 surrogate J43

Kisunla

donanemab · Amyloid-β (N3pG)

Aged PDAPP transgenic mice (amyloid plaques) treated with murine surrogate mE8c: dose- and effector-dependent plaque reduction

Lartruvo

olaratumab · PDGFRα

Human sarcoma xenografts (leiomyosarcoma, osteosarcoma) in nude mice treated with olaratumab, alone and with doxorubicin

Leqembi

lecanemab · Amyloid-β protofibrils

Tg2576 and APPArcSwe Alzheimer's mice with murine analog mAb158; lecanemab tested in vitro

Libtayo

cemiplimab · PD-1

Syngeneic colorectal tumor xenografts in huPD-1 knock-in mice treated with cemiplimab

Loqtorzi

toripalimab · PD-1

MC38 colon tumors in human PD-1 knock-in mice; melanoma xenograft in NSG mice with CTL transfer

Lucentis

ranibizumab · VEGF-A

Laser-induced choroidal neovascularisation (CNV) in monkeys; modified Miles vascular permeability assay

Margenza

margetuximab · HER2

HER2+ human breast cancer xenografts in mice, including hCD16A knock-in transgenic mice

Monjuvi

tafasitamab · CD19

SCID mouse subcutaneous xenografts of human Raji and RAMOS lymphoma; reduced tumor growth

Nemluvio

nemolizumab · IL-31RA

Clinical antibody in IL-31-induced itch model in cynomolgus monkeys; mouse surrogate BM095 in mite antigen-induced AD mouse model

Niktimvo

axatilimab · CSF-1R

In vitro human and monkey monocytes, CSF-1R-expressing CHO cells and human cancer cells; PD endpoints in monkey single- and repeat-dose studies

Nucala

mepolizumab · IL-5

Acute Ascaris suum challenge asthma model in cynomolgus monkeys; reduced pulmonary eosinophilia

Ocrevus

ocrelizumab · CD20

Human-derived cell lines in vitro; in vivo studies in cynomolgus monkeys only

Omvoh

mirikizumab · IL-23 p19

Mouse surrogate antibody LSN2479016 in two murine IBD models (CD4+ T-cell transfer colitis)

Opdivo

nivolumab · PD-1

Murine anti-PD-1 surrogate (4H2) in syngeneic mouse tumor models (MC38, Sa1N, J558 responsive)

Pasatru

garetosmab · Activin A

Garetosmab reduced heterotopic ossification in two conditional knock-in FOP mouse models

Penpulimab

penpulimab · PD-1

Human PD-1 knock-in mice (HuGEMM) bearing MC38 colon adenocarcinoma, dosed with penpulimab

Perjeta

pertuzumab · HER2

Human tumor xenografts (breast, prostate, NSCLC, ovarian; HER2 low or high) in mice treated with pertuzumab

Piasky

crovalimab · Complement C5

No PNH animal model; complement inhibition (CH50, free C5) in monkey PK/PD and repeat-dose studies plus in vitro RBC lysis

Portrazza

necitumumab · EGFR

Mouse xenografts of human NSCLC, pancreatic and colorectal tumour cell lines; tumour growth inhibition depending partly on EGFR status

Poteligeo

mogamulizumab · CCR4

SCID mouse xenografts of human CTCL (HH) and ATL (TL-Om1) cell lines

Praluent

alirocumab · PCSK9

APOE*Leiden.CETP mice on western diet, assessing lipid turnover and prevention of cardiovascular events

Praxbind

idarucizumab · Dabigatran

Dabigatran-anticoagulated bleeding models: rat tail bleeding, mouse intracranial haemorrhage, pig liver trauma

Prolia

denosumab · RANKL

Ovariectomized cynomolgus monkey model of postmenopausal osteoporosis

Raxibacumab

raxibacumab · B. anthracis protective antigen

Inhalational anthrax spore challenge in rabbits and non-human primates, alone and with antibiotics

Remicade

infliximab · TNF-α

Human TNFα transgenic mouse models and rhTNFα-challenged normal mice

Repatha

evolocumab · PCSK9

Cholesterol and LDL-C lowering in normal hamsters and monkeys

Rituxan

rituximab · CD20

B-cell depletion in normal cynomolgus monkeys (peripheral blood and lymphatic tissues)

Rystiggo

rozanolixizumab · FcRn

Mouse surrogate anti-FcRn mAb in an immune thrombocytopenia (ITP) disease model

Saphnelo

anifrolumab · IFNAR1

Mouse surrogate anti-IFNAR1 mAb in spontaneous SLE mouse model (prevented proteinuria)

Sarclisa

isatuximab · CD38

SU-DHL-8 non-Hodgkin lymphoma xenograft in SCID mice (in vivo proof of concept)

Siliq

brodalumab · IL-17RA

Mouse anti-IL-17RA surrogate antibodies in a mouse skin-inflammation model

Simponi

golimumab · TNF-α

Mouse arthritis model: single golimumab dose (1-30 mg/kg) delayed onset of clinical symptoms

Simulect

basiliximab · IL-2Rα (CD25)

In vitro IL-2 binding blockade on T-lymphocytes (human/primate cells) and human tissue binding; no in vivo model

Skyrizi

risankizumab · IL-23 p19

Human IL-23-induced mouse ear thickening (skin inflammation) model; in vitro IL-23 signalling and IL-17 inhibition

Soliris

eculizumab · Complement C5

Murine anti-rodent C5 surrogates in non-PNH mouse models (arthritis, lupus, airway inflammation, cardiac allograft)

Spevigo

spesolimab · IL-36R

Surrogate BI 674304 in imiquimod-induced and IL-36-induced mouse skin inflammation models

Stelara

ustekinumab · IL-12/23 p40

Marmoset experimental autoimmune encephalomyelitis (EAE) model with the clinical antibody

Sylvant

siltuximab · IL-6

Mouse xenograft models of human IL-6-producing tumours (e.g. H460 lung) with siltuximab; no MCD model

Synagis

palivizumab · RSV F protein

Cotton rat RSV infection model: lung virus titres reduced prophylactically and therapeutically at 5 mg/kg IM or IV

Takhzyro

lanadelumab · Plasma kallikrein

Carrageenan-induced rat paw oedema: dose-dependent inhibition, max 73% (SC) at 30 mg/kg

Taltz

ixekizumab · IL-17A

Surrogate anti-mouse IL-17 antibodies in mouse collagen-induced arthritis and EAE models

Tecentriq

atezolizumab · PD-L1

Syngeneic mouse melanoma and colorectal tumour models with murine/human chimeric atezolizumab; tumour growth reduced by at least 80%

Tepezza

teprotumumab · IGF-1R

Human tumour xenografts in nude mice: single 6 mg/kg IP dose down-regulated tumour IGF-1R (target engagement, not a TED model)

Tevimbra

tislelizumab · PD-1

Mouse xenograft tumour models engrafted with human PBMCs: anti-tumour efficacy against several tumour cell lines

Tezspire

tezepelumab · TSLP

Mouse surrogate M702 in OVA-induced asthma model: decreased airway hyperresponsiveness and BALF leukocytes

Tremfya

guselkumab · IL-23 p19

rhIL-23 challenge in mice: guselkumab attenuated induced serum IL-1α and G-CSF increases

Trogarzo

ibalizumab · CD4

SIV-infected rhesus monkeys: SIV viral load reduced up to day 10 despite neutralizing ADA

Tysabri

natalizumab · α4-integrin

Guinea pig EAE (MS model): natalizumab 3 mg/kg s.c. had beneficial effects on active EAE

Tzield

teplizumab · CD3

NOD mouse (spontaneous T1D) with anti-mouse CD3 surrogate: diabetes onset delayed ~5 weeks, incidence reduced ~30%

Ultomiris

ravulizumab · Complement C5

NOD-scid mice given human C5: >3-fold longer half-life and prolonged haemolysis inhibition vs eculizumab; no disease model

Unituxin

dinutuximab · GD2

Published SCID mouse xenografts: ch14.18 with human PBMCs and IL-2 prevented GD2+ melanoma growth

Unloxcyt

cosibelimab · PD-L1

In vitro only: binding, PD-1 reporter and human mixed lymphocyte reaction (increased IFN-γ); no in vivo model

Uplizna

inebilizumab · CD19

EAE and Sle1 autoimmune models in huCD19 transgenic mice: B-cell depletion, reduced autoantibodies and disease scores

Vectibix

panitumumab · EGFR

Tumour cell xenotransplants in mice: inhibition of tumour cell growth in vivo

Veopoz

pozelimab · Complement C5

Ex vivo hemolysis inhibition in serum from pozelimab-treated C5 humanized mice and normal monkeys

Voyxact

sibeprenlimab · APRIL

gddY IgA nephropathy mouse model with mouse surrogate mAb 4540; IgA reduction in healthy monkeys with sibeprenlimab

Vyepti

eptinezumab · CGRP

Capsaicin- or CGRP-induced dermal blood flow increase in rats, cynomolgus monkeys and rabbits

Vyloy

zolbetuximab · Claudin 18.2

Mouse xenograft models of human gastric cancer

Xolair

omalizumab · IgE

Skin test reactivity in ragweed-sensitised cynomolgus monkeys; otherwise in vitro studies

Yartemlea

narsoplimab · MASP-2

In vivo mouse model of TMA and ex vivo aHUS patient serum on human endothelial cells

Yervoy

ipilimumab · CTLA-4

MC-38 colon carcinoma in human CTLA-4 transgenic mice

Zinbryta

daclizumab · IL-2Rα (CD25)

In vitro inhibition of IL-2-induced proliferation and cytokine secretion in human and monkey primary lymphocytes

Zinplava

bezlotoxumab · C. difficile toxin B

Hamster and mouse C. difficile infection models with actoxumab+bezlotoxumab

Zynyz

retifanlimab · PD-1

Retifanlimab binding to peripheral T cells (flow cytometry) in cynomolgus monkey studies

Summary across all 118 monoclonal antibodies →